Stress signaling in breast cancer cells induces matrix comp. that promote chemoresistant metastasis

ABSTRACT: Metastatic progression remains a major burden for cancer patients and is associated with eventual resistance to prevailing therapies such as chemotherapy. Here, we reveal how chemotherapy induces extracellular matrix (ECM), wound healing and stem cell network in cancer cells via the c-Jun N-terminal kinase (JNK) pathway, leading to reduced therapeutic efficacy. We find that elevated JNK activity in cancer cells is linked to poor clinical outcome in breast cancer patients and is critical for tumor initiation and metastasis in xenograft mouse models of breast cancer. We show that JNK signaling enhances expression of the ECM and stem cell niche components osteopontin, also called secreted phosphoprotein 1 (SPP1), and tenascin C (TNC), that promote lung metastasis. We demonstrate that both SPP

SUBMITTER: Dr. Thordur Oskarsson 

PROVIDER: S-SCDT-EMM-2018-09003 | biostudies-other |

REPOSITORIES: biostudies-other